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S Iacob

Publications and source records attributed to S Iacob.

6 recordsLinked to original sources
PubMed2005

Predictors of death on the waiting list for liver transplantation characterized by a long waiting time.

The number of patients dying while on the liver transplantation (LT) waiting list (WL) has continued to increase in recent years as a result of severe shortage of organs. Therefore, it is important to evaluate the existing models that predict death on the WL and to determine the independent predictors of death. The study cohort comprised 152 adult patients listed for LT in our centre over a period of 2 years (January 2001 to January 2003). The 12-month survival rate has been calculated by Kaplan-Meier method. The survival analysis performed by Cox proportional hazard model has evaluated the three parameters which compose the model for end-stage liver disease (MELD) score. Forty-four patients (28.9%) died while listed for LT. The survival rate was 92% at 3 months, 80% at 6 months and 69% at 12 months. Median survival was not reached. MELD score was found to be an excellent predictor of death at 12 months on our WL--c-statistic (area under curve) 0.84. In our survival analysis, only international normalized (prothrombin) ratio (INR) and serum creatinine were identified as an independent predictors of death (P < 0.0001). A new simplified version of the MELD score, which does not include serum bilirubin, is proposed and its c-statistic as predictor for death on the WL at 12 months is 0.86, as good as the original MELD score, when evaluated on our list. There is a fourfold increase in mortality on our WL for LT between 3 and 12 months after the inclusion. A simplified version of the MELD score, using only serum creatinine and INR might be taken into account when predicting 12 months mortality on WL with longer waiting time, but it has to be confirmed by other prospective studies.

Adult↗
PubMed1997

Melatonin receptor antagonists that differentiate between the human Mel1a and Mel1b recombinant subtypes are used to assess the pharmacological profile of the rabbit retina ML1 presynaptic heteroreceptor.

We have identified subtype selective agonists, partial agonists and antagonists, which distinguish the human recombinant Mel1a and Mel1b melatonin receptors expressed in COS-7 cells. Melatonin receptor agonists showed higher affinity for competition of 2-[125I]-iodomelatonin binding for the Mel1b than the Mel1a melatonin receptor. The dissociation constants (Ki) of 16 agonists determined on the recombinant human Mel1a and Mel1b melatonin receptor subtypes showed a significant correlation (r2 = 0.85, slope = 0.97, P < 0.0001, n = 16). However, six agonists showed 10 to 60 fold higher affinity for the Mel1b melatonin receptor as indicated by the affinity selectivity ratios (Mel1a/Mel1b) [8-methoxy-2-acetamidotetraline (11); S20098 (14); 8-methoxy-2-propionamidotetraline (20); 6, 7 di-chloro-2-methylmelatonin (21); 6-chloromelatonin (57); 6-methoxymelatonin (59)]. Dissociation constants for competition of 11 partial agonists and antagonist for 2-[125I]-iodomelatonin binding were between 15.5 (luzindole, pKi: 7.7) to 362 (4-phenyl-2-chloroacetamidotetraline, pKi: 9.1) fold higher for the Mel1b than for the Mel1a melatonin receptor. The lack of correlation between the pKi values (r2 = 0.23, P > 0.1, n = 11) strongly suggest that the two human melatonin receptor subtypes can be distinguished pharmacologically. The partial agonist: 5-methoxyluzindole (pKi: 9.6) and the competitive melatonin receptor antagonists: GR128107 (pKi: 9.6), 4-phenyl-2-chloroacetamidotetraline (pKi: 9.1), 4-phenyl-2-acetamidotetraline (pKi: 8.9) and 4-phenyl-2-propionamidotetraline (pKi: 8.8) are selective Mel1b melatonin receptor analogues as their affinity selectivity ratios (Mel1a/Mel1b) are bigger than 100. We conclude that the 40% overall amino acid difference in the sequence of the human recombinant Mel1a and Mel1b melatonin receptors is reflected in distinct pharmacological profiles for the subtypes. We compared the pharmacological profile of the presynaptic ML1 melatonin heteroreceptor of rabbit retina mediating inhibition of the calcium-dependent release of dopamine to that of the recombinant Mel1a and Mel1b melatonin receptors. Melatonin inhibited [3H]dopamine release by 50% (1C50) at 20 pM with a maximal inhibitory effect (80%) at 1 nM. The partial agonists, i.e., N-acetyltryptamine (1C50 5.6, maximal inhibition 55%) and 5-methoxyluzindole (1C50: 1.3, maximal inhibition 40%) showed various degrees of efficacy while none of the competitive melatonin receptor antagonists did inhibit [3H]dopamine release on their own. The potency (1C50) of full melatonin receptor agonists significantly correlated with their affinity to compete for 2-[125I]-iodomelatonin binding to either the Mel1a (r2 = 0.76, slope = 0.77, P < 0.0001, n = 17) or Mel1b (r2 = 0.63, slope = 0.75, P < 0.001, n = 17) human melatonin receptors. By contrast, the apparent dissociation constants (KB) for partial agonists and antagonists to antagonize the inhibition of [3H]dopamine release mediated by activation of the ML1 heteroreceptor by melatonin, significantly correlated with the affinity constants (Ki) for 2-[125I]-iodomelatonin binding determined of the Mel1b (r2 = 0.77, slope = 0.55, P < 0.001; n = 11) but not the Mel1a (r2 = 0.27, P < 0.1, n = 11) subtype. Together these results demonstrate that the pharmacological profile of the human recombinant Mel1b melatonin receptor is similar to that of the functional presynaptic melatonin heteroreceptor of rabbit retina, which we referred as an ML1B subtype. We conclude that the selective Mel1b melatonin partial agonists and antagonists described here can be used to identify melatonin receptor subtypes in native tissues and to search for subtype selective analogues with therapeutic potential.

Animals↗
PubMed1989

[Research on phagocytosis].

A problem of particular importance, but also particularly difficult, is the investigation of the phagocytic system, considering its implication in various aspects of pathology. This has determined the authors to present the major modalities for the investigation of phagocytosis. They recommend as a diagnostic method for garnulocytopathies (including a series of metabolic abnormalities. Of the leucocytes with implications for the bactericidal capacity), a testing of leucocyte bactericidal capacity. The test with nitroblue tetrazolium is also recommended, for the screening and differential diagnosis of fever conditions of infectious origin and other etiologies.

Humans↗
PubMed1988

Characterization of hydrazine-stimulated proteolysis in human erythrocytes.

The ability of hydrazine, acetylphenylhydrazine, methylhydrazine, and phenylhydrazine to stimulate proteolysis in red cells has been characterized. All four hydrazines effectively stimulated proteolysis in red cells and in hemolysate as evidenced by a two- to threefold increase in the rate of tyrosine release. The rate of tyrosine release varied linearly with time, increased with increasing concentration of hydrazine, and also increased as a function of hematocrit. The rank order for stimulation of proteolysis in red cells was phenylhydrazine greater than methylhydrazine greater than hydrazine approximately equal to acetylphenylhydrazine. Inhibitors of glycolysis in red cells only minimally (13-27%) decreased the rate of tyrosine release stimulated by the different hydrazines. Agents which diminished electron transport decreased the rate of tyrosine release. NADP inhibited the rate of tyrosine release stimulated by hydrazine, methylhydrazine, and acetylphenylhydrazine by approximately 36 to 41%; 2'-AMP was less effective. The rate of tyrosine release resulting from insult by the hydrazines was increased slightly by methylene blue, moderately inhibited (approximately 10 to 27%) by the chelator o-phenanthroline and inhibited approximately 30 to 40% by N-ethylmaleimide. Use of an oxygen-depleted atmosphere (N2) increased slightly the rate of tyrosine release stimulated by the hydrazines; in contrast, carbon monoxide decreased proteolysis stimulated by hydrazine, methylhydrazine, and acetylphenylhydrazine by approximately 50%. Although the antioxidants dimethylfuran, dimethylthiourea, and methylsulfoxide failed to diminish proteolysis stimulated by the hydrazines, N-acetylcysteine exerted a protective effect, decreasing hydrazine-stimulated tyrosine release in red cells approximately 30 to 50%. Inclusion of 3-amino-1,2,4-triazole in the incubation failed to increase further the rate of hydrazine-stimulated proteolysis. These data suggest that more reactive free radicals generated from the hydrazine are responsible for protein damage, that damaged protein (hemoglobin) is degraded via proteolysis, and that an ATP-independent process primarily participates in the degradation of abnormal proteins in the red cell. Thus, proteolytic enzymes present in the erythrocyte appear to exert a protective effect against cellular damage through the removal of abnormal proteins generated as a consequence of xenobiotic insult. The ability of proteolytic enzymes to recognize and degrade abnormal proteins may be of importance in using protein (hemoglobin)-xenobiotic adducts to assess exposure to toxic agents (risk assessment).

Adenosine Triphosphate↗
PubMedDate not supplied

[Immunologic research in pediatrics].

The child, in his ontogenesis, repeats the phylogenetic evolution of the immune processes. The immunologic maturation gradually appears, the process having a definite duration. The immunologic maturation seems to be parallel to the maturation of other physiological processes. The immune system of the child is different from that of the adult, and the development features of his immune reactivity will give a specific evolution to his morbid manifestations.

Antibody Formation↗